Cross-neutralization of influenza A viruses mediated by a single antibody loop
Identifieur interne : 000B33 ( Main/Merge ); précédent : 000B32; suivant : 000B34Cross-neutralization of influenza A viruses mediated by a single antibody loop
Auteurs : Damian C. Ekiert [États-Unis] ; Arun K. Kashyap [États-Unis] ; John Steel [États-Unis] ; Adam Rubrum [États-Unis] ; Gira Bhabha [États-Unis] ; Reza Khayat [États-Unis] ; Jeong Hyun Lee [États-Unis] ; Michael A. Dillon [États-Unis] ; Ryann E. O Eil [États-Unis] ; Aleksandr M. Faynboym [États-Unis] ; Michael Horowitz [États-Unis] ; Lawrence Horowitz [États-Unis] ; Andrew B. Ward [États-Unis] ; Peter Palese [États-Unis] ; Richard Webby [États-Unis] ; Richard A. Lerner [États-Unis] ; Ramesh R. Bhatt [États-Unis] ; Ian A. Wilson [États-Unis]Source :
- Nature [ 0028-0836 ] ; 2012-09-27.
Abstract
Immune recognition of protein antigens relies on the combined interaction of multiple antibody loops, which provide a fairly large footprint and constrain the size and shape of protein surfaces that can be targeted. Single protein loops can mediate extremely high-affinity binding, but it is unclear whether such a mechanism is available to antibodies. Here we report the isolation and characterization of an antibody called C05, which neutralizes strains from multiple subtypes of influenza A virus, including H1, H2 and H3. X-ray and electron microscopy structures show that C05 recognizes conserved elements of the receptor-binding site on the haemagglutinin surface glycoprotein. Recognition of the haemagglutinin receptor-binding site is dominated by a single heavy-chain complementarity-determining region 3 loop, with minor contacts from heavy-chain complementarity-determining region 1, and is sufficient to achieve nanomolar binding with a minimal footprint. Thus, binding predominantly with a single loop can allow antibodies to target small, conserved functional sites on otherwise hypervariable antigens.
Url:
DOI: 10.1038/nature11414
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<front><div type="abstract" xml:lang="eng">Immune recognition of protein antigens relies on the combined interaction of multiple antibody loops, which provide a fairly large footprint and constrain the size and shape of protein surfaces that can be targeted. Single protein loops can mediate extremely high-affinity binding, but it is unclear whether such a mechanism is available to antibodies. Here we report the isolation and characterization of an antibody called C05, which neutralizes strains from multiple subtypes of influenza A virus, including H1, H2 and H3. X-ray and electron microscopy structures show that C05 recognizes conserved elements of the receptor-binding site on the haemagglutinin surface glycoprotein. Recognition of the haemagglutinin receptor-binding site is dominated by a single heavy-chain complementarity-determining region 3 loop, with minor contacts from heavy-chain complementarity-determining region 1, and is sufficient to achieve nanomolar binding with a minimal footprint. Thus, binding predominantly with a single loop can allow antibodies to target small, conserved functional sites on otherwise hypervariable antigens.</div>
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